A chromosome pulled from the flowers of Arabidopsis thaliana (green and white) unspools to reveal DNA (blue) coiled around packaging-proteins called histones (purple). The direction of epigenetic changes by genetic features begins as the RIM transcription factor (pink) docks on a corresponding DNA sequence (pink). Once docked, the RIM transcription factor directs methylation machinery to tack methyl groups (orange) onto specific nearby cytosines (orange). Click here for a high-resolution image. Credit: Salk Institute.

All the cells in an organism have the exact same genetic sequence. What differs across cell types is their epigenetics—meticulously placed chemical tags that influence which genes are expressed in each cell. Mistakes or failures in epigenetic regulation can lead to severe developmental defects in plants and animals alike. This creates a puzzling question: If epigenetic changes regulate our genetics, what is regulating them?

Scientists at the Salk Institute have now used plant cells to discover that a type of epigenetic tag, called DNA methylation, can be regulated by genetic mechanisms. This new mode of plant DNA methylation targeting uses specific DNA sequences to tell the methylation machinery where to dock. Prior to this study, scientists had understood only how DNA methylation was regulated by other epigenetic features, so the discovery that genetic features can also guide DNA methylation patterns is a major paradigm shift.

Leukemia starts when mutations in blood-forming cells disrupt the balance between growth and differentiation. Patients with entirely different genetic changes show strikingly similar patterns of gene activity and can respond to the same drugs. What invisible thread could make so many mutations behave the same way?

The authors looked into high-resolution microscope and saw something no one expected: leukemia cell nuclei shimmered with a dozen bright dots – tiny beacons missing from healthy cells.

Those dots weren’t random. They contained large amounts of mutant leukemia proteins and drew in many normal cell proteins to coordinate activation of the leukemia program. The dots were new nuclear compartments formed by phase separation, the same physical principle that describes why oil droplets form in water. The team named this new compartment, “coordinating bodies,” or C-bodies.

Inside the nucleus, these C-bodies act like miniature control rooms, pulling together the molecules that keep leukemia genes switched on. Like drops of oil collecting on the surface of soup, they appear when the cell’s molecular ingredients reach just the right balance.

Even more surprising, cells carrying entirely different leukemia mutations formed droplets with the same behavior. Although their chemistry differs, the resulting nuclear condensates perform the same function, using the same physical playbook.

A new quantitative assay confirmed it. These droplets are biophysically indistinguishable – like soups made from different ingredients that still simmer into the same consistency. No matter which mutation started the process, each leukemia formed the same kind of C-body.

The team confirmed the finding across human cell lines, mouse models and patient samples. When they tweaked the proteins so they could no longer form these droplets – or dissolved them with drugs, the leukemia cells stopped dividing and began to mature into healthy blood cells.